CN104582849B - Multiple reaction chambers in testing cassete - Google Patents
Multiple reaction chambers in testing cassete Download PDFInfo
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- CN104582849B CN104582849B CN201380034569.3A CN201380034569A CN104582849B CN 104582849 B CN104582849 B CN 104582849B CN 201380034569 A CN201380034569 A CN 201380034569A CN 104582849 B CN104582849 B CN 104582849B
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- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
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- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6806—Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay
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- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/5306—Improving reaction conditions, e.g. reduction of non-specific binding, promotion of specific binding
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- B01L2300/0627—Sensor or part of a sensor is integrated
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- B01L2300/0861—Configuration of multiple channels and/or chambers in a single devices
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- B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
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Abstract
The present invention provides a kind of fluid test system, and it includes multiple test chamber, multiple access road and access road is connected to the fluid network of other chamber one or more.Each test chamber in multiple test chambers is characterised by length and hydraulic diameter.The length of each test chamber is generally parallel directed at gravitational vectors.Each test chamber has only one opening, and this opening is arranged along the length of corresponding test chamber.It addition, the only one access road that each test chamber is connected in multiple access road via its corresponding opening.
Description
Technical field
Embodiments of the invention relate to clinical diagnosis field of tool.
Background technology
In view of molecular testing and the complexity of the automatization of immunoassay, lack and foot is provided
Enough performances are so as to be used for the product close to patient's testing setup.Typical molecular testing bag
Include various procedures, crack to extract DNA including the correct dose of reagent, Sample introduction, cell
Or RNA, purification step and amplification are for its follow-up detection.Even if existing and making these
During central laboratory's robot platform of some automatization, but for requiring short turnover
For many tests of time, central laboratory can not provide knot in required time requirement
Really.
But, it is difficult to provide accurate reliable results with rational cost in clinical settings
System.In view of the complex characteristics of various molecular testing technology, without being carefully controlled
If test parameter or environmental condition are undesirable, then error probably occurs in result.Example
As, due to the external source reasons for its use of DNA, and make having for round pcr
High entrance barrier is there is in instrument for clinical diagnostic applications.Feelings in special pathogen test
Under condition, the main source of pollution is to perform in pipet, pipe or general laboratory equlpment
The result of reaction before.It addition, use the molecular engineering detecting microbial pathogens possible
Produce false negative.False negative may be derived from such as: processes suppression polymerase chain improperly anti-
Answer the reagent of (PCR), such as hemoglobin, urine or expectorant;Less efficiently discharge from cell
DNA;Or less efficiently extract and purification DNA or RNA.
Molecular engineering has abnormal sensitive level under the concentration lower than reference method before
The fact makes to be very difficult to while avoiding false positive error calls obtain clinically relevant knot
Opinion.In order to minimize this problem, especially for detection pathogen microorganism, test should
There is quantization ability.Therefore, have increasing need for performing multichannel test and hot-wire array, with combination
Enough data draw the conclusion be sure oing.As an example, the survey of existing PCR-based
One major limitation of examination is to carry out the amplification of different target gene simultaneously.Although it is all
As the technology of microarray provides the most much higher road ability, but their major limitation is
The speed obtaining result is low, and this has no positive impact generally for for case control.
Summary of the invention
The present invention provides a kind of fluid test system, and it includes multiple test chamber.Simultaneously flow
Body controls each test position can reduce the testing time, and improves at multiple test positions it
Between obtain the probability of repeatable result.
In one embodiment, single port fluid test system includes multiple test chamber, each
Test chamber is characterised by length and hydraulic diameter.Each test chamber in multiple test chambers
Room all has only one opening, and this opening is arranged along the length of corresponding test chamber.Fluid
Test system also includes the first access road and multiple divided fluid stream element.Divided fluid stream element will
Original liquid along the first access road flowing is diverted in multiple second access road.Multiple
Each test chamber in test chamber is connected to multiple second entrance via its corresponding opening
Only one the second access road in passage.
The present invention describes a kind of illustrative methods.The method includes: make the liquid edge of primary quantity
The first access road flowing of single port fluid test system.The liquid of primary quantity is divided to
Multiple second access roades, each second access road is connected to multiple test chamber, Qi Zhongduo
Each test chamber in individual test chamber has the only one of the length setting along chamber and opens
Mouthful.The method also includes: each test chamber is filled with the liquid of final quantity, each test
Final quantity in chamber is substantially identical, and the sum of the liquid of the final quantity of each test chamber
Liquid equal to primary quantity.
In another embodiment, fluid test system includes multiple test chamber, multiple entrance
Passage and access road is connected to the fluid network of other chamber one or more.Test chamber
Room each has length and hydraulic diameter.The length of each test chamber is with gravitational vectors substantially
It is directed at abreast.Each test chamber has only one opening, and this opening is surveyed along correspondence
The length of examination chamber is arranged.It addition, each test chamber is connected to via its corresponding opening
Only one access road in multiple access roades.
The present invention describes another kind of illustrative methods.The method includes: flow liquid through multiple
Access road, each access road is connected to multiple test chamber.The length of each test chamber
Generally parallel it is directed at gravitational vectors, and each test chamber has only one and opens
Mouthful, this opening is arranged along the length of chamber.The method also includes: by multiple test chambers
Each test chamber be filled with liquid, until threshold quantity.The method also includes: pass through entrance
Passage by liquid from each test chamber sucking-off, to leave scheduled volume in each test chamber
Liquid.
The present invention describes another kind of illustrative methods.The method includes: make first liquid flow through
First access road, the length that this first access road is connected to along test chamber is high first
The first opening arranged at degree.The length of test chamber is generally parallel directed at gravitational vectors.
The method also includes: test chamber is filled with first liquid, until first threshold amount.Pass through
First liquid from test chamber sucking-off, and is left in test chamber by the first access road
The first liquid of one scheduled volume.The method also includes: make second liquid flow through the second access road,
This second access road is connected to second arranged at the second height along the length of test chamber
Opening.Second height is more than the first height.The method also includes: test chamber is filled with
Two liquid, until Second Threshold amount.By the second access road by second liquid from test chamber
Sucking-off, and in test chamber, leave the second liquid of the second scheduled volume.
The present invention describes another kind of illustrative methods.The method includes: flow liquid through multiple
Each passage in passage, until arranging liquid sensing region in each channel, thus
The liquid of scheduled volume is set in each passage in multiple passages.The method also includes: make multiple
The liquid of the only scheduled volume in each passage in passage is flowed into the phase coupled with each passage
In the chamber answered.
Accompanying drawing explanation
The accompanying drawing of the part being incorporated herein and form description shows the enforcement of the present invention
Example, and also it is used for explaining the principle of the present invention together with description, so that association area
Technical staff can manufacture and use the present invention.
Fig. 1 is the schematic diagram of the testing cassete system according to an embodiment.
Fig. 2 shows the side view of the testing cassete system according to an embodiment.
Fig. 3 shows the test chamber according to an embodiment.
Fig. 4 A-C shows the operation of the test chamber according to an embodiment.
Fig. 5 shows the multiple test chambers according to an embodiment.
Fig. 6 A-C shows the another kind of operation of the test chamber according to an embodiment.
Fig. 7 shows the another kind of test chamber according to an embodiment.
Fig. 8 shows the multiple test chamber of the another kind according to an embodiment.
Fig. 9 shows the multiple test chamber of the another kind according to an embodiment.
Figure 10 shows the testing cassete system being in analyzer according to an embodiment.
Figure 11-14 shows the exemplary chamber fill method according to an embodiment.
Embodiment of the invention will be described with reference to drawings.
Detailed description of the invention
Although discussing specific structure and arrange, but it is to be understood that this being only used to figure
Show descriptive purpose.Those skilled in the relevant art are it will be appreciated that without departing from the present invention's
In the case of spirit and scope, other structure can be used and arrange.For related-art technology
It is evident that the present invention can be also used for other application various for personnel.
It should be noted that in the description to " embodiment ", " embodiment ", " exemplary reality
Execute example " etc. reference show that described embodiment can include specific feature, structure or characteristic,
But each embodiment can include specific feature, structure or characteristic.Additionally, so
Phrase be not necessarily related to identical embodiment.It addition, it is specific when describing relatively with embodiment
When feature, structure or characteristic, in those skilled in the art's cognitive range, regardless of whether
It is expressly recited, such feature, structure or characteristic can be realized with other embodiments relatively.
Embodiment as herein described relates to testing cassete system, and it is used for performing various molecular testing,
Such as immunoassay, PCR, DNA hybridization etc..In one embodiment, testing cassete and execution
All parts needed for such test are formed integrally as single disposable package piece.Testing cassete
Can be configured to be analyzed by externally measured system, to provide to enter with in testing cassete
The data that the reaction of row is correlated with.In one embodiment, testing cassete includes having transparent window
Multiple test chambers, to utilize each test chamber to perform optical detection.
In one example, single testing cassete can be used to utilize the sample specified to perform immunity point
Analysis array.Testing cassete comprises all necessary buffer agent, reagent and marks being maintained at and sealing in chamber
Signing, to perform immunoassay, this sealing chamber is integrally coupled in this box.
In another example, single testing cassete can be used to perform PCR.DNA can be through
It is purified from the remainder of sample by the filter being attached in testing cassete.Sample can lead to
Crossing filter extrusion, DNA can be removed by the eluting liquid simultaneously separately stored, and
DNA is taken in another chamber, to start temperature cycles process.
One major limitation of molecular diagnosis instrument is the problem relevant to pollutant, such as, intersect
Pollution, carryover contamination etc..Embodiment as herein described substantially eliminates sample pair by design
The pollution of instrument.
In one embodiment, testing cassete provides the self-contained liquid sealed during manufacture process.
Reagent with sample not any part with environment or instrument contact.This feature pair of testing cassete
Also it is important for many laboratorys and hospital, disposes safely after using at product
These products.
According to an embodiment, in order to perform hot-wire array, testing cassete includes multiple test chamber,
These test chambers are designed to be convenient for measuring the optics of the content in each test chamber
Characteristic.Such as, each test chamber includes transparent window, to allow content therein
Carry out fluorescence or absorbance research.It addition, the design of the fluid placement of each test chamber is permissible
Each chamber is allowed to be filled into identical level while using single pumping source.
Describe and each parts of the testing cassete system including test chamber herein with reference to accompanying drawing
Relevant further details.The diagram that should be appreciated that each physical unit is not restricted
, without departing from the spirit or scope of the present invention, the phase that the description herein is specified
Skilled person will appreciate that of field, pass rearranges or otherwise changes any parts
Various modes.
Fig. 1 shows the exemplary testing cassete with test chamber array according to an embodiment
System 100.Although in this article by the structure with reference to exemplary testing cassete system 100, but
It will be recognized by those skilled in the art, the embodiment of test chamber as herein described may be used for
Any amount of test system type and structure.
Testing cassete system 100 includes box housing 102.Other parts are equally considered to comprise
In testing cassete system 100, such as analyzer module or various driving part, such as pump or add
Hot device.
Box housing 102 includes multiple fluid passage, chamber and reservoir.Such as, box housing 102
Can include multiple storage chamber 116, these storage chambers can comprise will analyzed or PCR
The various buffer agents used in scheme or other reagent.Storage chamber 116 can be pre-filled with
Plurality of liquid so that end user need not testing cassete system 100 is being put into analyzer
Storage chamber 116 was filled before in.In another example, reagent is being put into storage chamber
It was lyophilizing before in room 116.Box housing 102 can also include the side along box housing 102
One or more process chamber 124a-b that face is connected with fluid passage.Process chamber 124a-b
May be used for various process and/or garbage application.
According to an embodiment, sample is incorporated in box housing 102 via sample port 114.
In one example, sample port 114 receives solid-state, semisolid or liquid sample.At another
In individual embodiment, box housing 102 includes the more than one entrance guiding sample.
Each chamber and passage around box housing 102 can use covering 118,126,127
Seal with 128.Covering can be can the film of fluid in seal box housing 102.
In another example, covering can be plastic front board.In one example, one or many
Individual covering is transparent.It addition, one or more coverings can by thermal control, with
Heating part in housing 102.
The testing cassete system 100 of integration allows user that sample is placed into such as sample port
In 114, then testing cassete system 100 is put in analyzer.In many embodiment,
Interact via with analyzer, including such as purification, crack, mix, bond, label
And/or the pending reactions steps of detection all can perform in testing cassete system 100, and
Need not any end user intervene.It addition, because all of liquid maintains a seal against
In testing cassete system 100, so after completion of testing, testing cassete system 100 can be from dividing
Parser removes, and carries out safe process, without contamination analysis device.
Fig. 2 shows the side view of the box housing 102 according to an embodiment.List box shell
The explanation of body 102, to describe the feature being likely to be of on box housing 102, but should not limit
Make setting or the dimensional characteristic of these features.
Fig. 2 shows fluid network and a series of ports extending in box housing 102.Fluid
Network may be coupled to the storage chamber 116 of box housing 102 and/or processes in chamber 124a-b
One or more.These chambers can be arranged on box housing 102 with the side shown in Fig. 2
On relative side.In one embodiment, fluid network is also connected to a series of test chamber
216。
Each fluid passage may be designed to terminate at port, and this port will be with housing
The port on movable transfer module (not shown) or valve region in 102 have a common boundary.According to one
Embodiment, multiple ports 210 allow fluid to flow to any chamber of housing 102.Multiple ports
210 may serve as the arrival end that liquid is inhaled in the internal chamber in box housing 102
Mouthful, or may serve as liquid and be discharged to the fluid network of box housing 102 from internal chamber
Outlet port.Such as, liquid can be pressurized, to flow through the right number in fluid port 210
Second port, and be flowed in the most remote right side test chamber 216.Additionally, liquid is permissible
It is sucked back into fluid port from the most remote right side test chamber 216 via the vacuum pressure applied
In right several second port in 210.
The shape of test chamber 216 can be similar to such as centrifuge tube.In one embodiment,
Liquid can be inhaled in test chamber 216, be loaded previously in each test chamber
Reagent mixing.Such as, what each test chamber can be loaded with for PCR process is different
Primer and probe, and liquid can be inhaled into each test chamber, with in each chamber
Form different mixture.Reagent can be lyophilized before being loaded in test chamber 216.
In another embodiment, test chamber 216 is additionally operable to sample detection.Can utilize and analyze
External light source and photoelectric detector that device couples detect, and testing cassete system 100 is placed on this
In analyzer.Therefore, any wall of test chamber 216 or covering can be transparent, with
Allow to carry out optical detection.In one example, photoelectric detector is under one or more wavelength
Measure the absorbance by the liquid in test chamber.In another example, photoelectric detector
Measure the fluorescence signal generated by the fluorescent chemicals in test chamber.In one embodiment,
Fluorescence measurement is carried out below test chamber 216.Test chamber 216 goes for other inspection
Survey device, such as electrochemistry, electromechanics, surface plasmon resonance device etc..
According to an embodiment, in the upstream of test chamber 216 it is observed that one group less
Passage expansion section 214.Passage expansion section 214 can serve as liquid sensing region.Therefore, logical
Expansion section, road 214 can be used for detecting in passage expansion section 214 together with external optical probe
Whether there is liquid.This determine other function that can be used to activate testing cassete system 100.
In another embodiment, passage expansion section 214 can include the sensor of integration, such as
Patterning electric resistance sensor, to indicate existence or the flow of fluid.It addition, expand at some passage
The existence of the liquid in the corresponding test chamber 216 of optical signalling monitoring detected at big portion 214.
Liquid sensing region in passage expansion section 214 can be used to set to be metered to each
The scheduled volume of the liquid in test chamber 216.Such as, liquid can individually or simultaneously by
It is pressurized in each passage, until liquid arrives the liquid sensing region in each passage.So,
Each passage can comprise the liquid of substantially identical amount, and this liquid filling channel is up to passage
Expansion section 214.Afterwards, according to an embodiment, each passage can be individually or simultaneously
It is pressurized to force the liquid of scheduled volume to be downwardly into each test chamber 216.
According to an embodiment, multiple chambers 231 that are pre-mixed can also be arranged on test chamber
The upstream of 216.It is pre-mixed chamber 231 and can include dry chemical, that such as freeze or freeze
Dry analyte.In another example, it is pre-mixed chamber 231 and includes dry chemistry pearl
Or biological sample.Biological sample can carry out lyophilizing in being pre-mixed chamber 231.Such
Biological or chemical compound can be stored in the most for a long time and be pre-mixed chamber 231
In.According to an embodiment, it is pre-mixed may be sized in order to spy of chamber 231
Not coordinating the size of dry chemistry pearl, general diameter is of about several millimeters.At an example
In, it is attracted to the fluid of reaction chamber 216 and is stored in the sample being pre-mixed in chamber 231
Mixing.
According to an embodiment, at the low portion of box housing 102 in fig. 2, in test
It is provided with optics below chamber 216 and enters region 240.Optics enters region 240 and is designed to
It is all substantial transparent to all wavelengths used during optical detection process.At an example
In, each single test chamber 216 has the optics of himself and enters region.At another
In example, single optics enters region and extends across multiple test chamber 216.
According to an embodiment, the side of box housing 102 also illustrates that pressure port 236
With discharge port 234.According to an embodiment, pressure port 236 may be coupled to outside pressure
Power source, for applying positive or negative pressure differential in the entire system.Discharge port 234 can
To lead to air or to be connected to another pressure source.Such as, positive pressure difference can be applied to one
Individual port, negative pressure differential is applied to another port simultaneously, so that liquid moves more quickly
Passage by the connection of system.
One film or multiple film can be arranged on this series of test chamber 216.Film is permissible
Sufficiently thin still to provide sufficiently sealing, also allow for the content in test chamber 216 simultaneously
Carry out more easily via external source heating and/or cooling down.Such as, film can have by heat
Any one or combinations thereof in electric installation, resistance heater and pressure air-flow and carry out thermal control
The surface of system.In one example, film is polymeric film, and its thickness is less than 100 microns.?
In one example, the thermal conductivity of film is more than 1W/mK.
Fig. 3 illustrates in greater detail the view of the test chamber 216 according to an embodiment.Survey
Examination chamber 216 includes the single opening 304 arranged along the length of test chamber 216, and this is opened
Mouth is connected to access road 302.Test chamber 216 also has curved bottom wall 306.The bending end
Portion's wall 306 can be transparent, to allow to carry out optical detection below test chamber 216.
Test chamber 216 has sufficiently large hydraulic diameter, is large enough so that action of gravity impact and surveys
Fluid flowing in examination chamber 216.Therefore, test chamber 216 is aligned so that its length
Substantially parallel with gravitational vectors.Due to this layout, liquid is affected by action of gravity,
And filled chamber bottom-up.
Test chamber 216 can accommodate reagent 308.Reagent 308 can have any quantity
Reagent.Reagent 308 can exist in liquid form, or is lyophilizing globule.Reagent 308
It is resuspended in being flowed in the liquid in test chamber 216.In another example, reagent
308 are stored in and are pre-mixed in chamber 231, in order to mix with the fluid of test chamber 216 upstream
Close.
Access road 302 is connected to test chamber 216 via opening 304.Access road 302
The passage can being integrated in the multiple passages in box housing 102.Access road 302
There is provided and be used for what fluid was flowed in test chamber 216 and was sucked out from test chamber 216
Fluid path.
In one embodiment, the width width of the width ratio access road 302 of opening 304.Relatively
Wide opening makes liquid enter test chamber 216 more controllably, and also reduces
The size of the drop that liquid is produced by liquid when entering test chamber 216 by opening 304.This
Each factor in a little factors reduces liquid between two lateral sidewalls of test chamber 306
Form the probability of meniscus.Meniscus is formed such that the amount of the liquid being difficult to control in chamber,
And cause the formation of bubble.Bubble may destroy any life carried out in test chamber 216
Thing processing procedure, and cause optical measurement error.
According to an embodiment, Fig. 4 A-C shows the exemplary operation of test chamber 216.
In Figure 4 A, during the liquid of scheduled volume is arranged on access road 302.The liquid of this scheduled volume
It is assigned in test chamber 216 by opening 304, as shown in Figure 4 B.Liquid can be such as
It is allocated via the pressure differential generated.
In one example, the amount being metered into the liquid in test chamber 216 is selected such that
The liquid level of gained is at height h or lower section, and wherein h is that opening 304 is to test chamber
Distance bottom 216.The liquid 402 of gained is as shown in Figure 4 C.Therefore, test chamber 216
Top section in any gas freely escape via opening 304.
The liquid meter of scheduled volume to test chamber 216 will allow this program via single pressurization
Event and carry out.Therefore, the coordination of the filling of parallel multiple test chambers is simplified.
Fig. 5 shows the exemplary arrangement of the multiple test chambers 216 according to an embodiment.
Single connection entrance (or port) 502 is shown as being connected to by multiple test chambers 216
The such as fluid network of testing cassete system 100.In one embodiment, single entrance 502
Receiving single port, wherein this single port is the only outside opening of fluid system.
In an example shown, because being provided solely for single entrance 502 in order to be arrived by liquid meter
In multiple test chambers 216, so fluid passage includes multiple corridor diversion device 504a-c.Logical
The geometry of road diverter 504a-c might be chosen such that the half of the liquid of arrival along
One path flowing, and second half flows along another path.Alternatively,
This geometry can be chosen in order to form dividing of any ratio between the passage of two gained
Flowing liquid.Multiple test chambers 216 need not the most whole straight alignment, but can
With to keep the total path length between single entrance 502 and each test chamber 216 equal
Any mode is arranged.Equal path simplifies the liquid meter of the amount of will be controlled by and arrives
Program in each test chamber 216.
Corridor diversion device 504a-c helps the liquid meter of equivalent to each test chamber 216
In.For example, it is possible to introduce the liquid of 80 μ L via single connection entrance 502.In succession wearing
After crossing corridor diversion device 504a, 504b and 504c, the liquid of 10 μ L will be metered into each
In test chamber 216.Although this example considers that each corridor diversion device 504a-c is 50/50
Fluid diverter, but need not be this situation, can be real between test chamber 216
The gained Fluid Volume of what ratio incumbent.
Passage shown in Fig. 5 is arranged and is represented closed fluid system, and it allows via single pressurization thing
Part implements metering more easily.Such as, the normal pressure being applied to single connection entrance 502 can
To be used in the liquid meter of scheduled volume to each test chamber 216, as before with reference to figure
Described in 4A-C.
Fig. 6 A-C describes the exemplary operation of the test chamber 216 according to an embodiment.
In fig. 6, test chamber 216 is filled with liquid, until the height bigger than height h.Can
To apply normal pressure, so that chamber 216 is filled until this point.In one embodiment, this is
System can include pressure transducer and/or actuator, to control pressure applied, and senses
When liquid has arrived at threshold quantity.
In fig. 6b, apply negative pressure, and by access road 302 by liquid from test
Sucking-off in chamber 216.The speed that negative pressure can be applied to so that fluid is sucked out is faster than fluid
Flow into speed during test chamber 216.
In figure 6 c, liquid is sucked out, until the liquid level in test chamber 216 declines
To height below h.After removing negative pressure, the liquid of scheduled volume 602 is retained in test chamber
In room 216.The definite volume of scheduled volume 602 depends on the height h of opening 304, test chamber
The hydraulic diameter of room 216 and the pressure applied during drawing liquid.Utilize this process,
Can only by single access road 302 by the liquid meter of amount of calculation to test chamber 216
In.Such as, the amount staying liquid in the chamber can be by the surface tension on gravity and liquid
The position overcoming the negative pressure being applied to passage is determined.In one example, from test chamber
In room 216, the speed of sucking liquid is sufficiently fast so that be not likely to be present in test chamber 216
In reagent by access road 302 sucked back.Highly h can be for test chamber 216
Various designs are adjusted, to regulate the amount of the liquid stayed in test chamber 216.
Fig. 7 shows the embodiment of multichannel chamber 702.Two access road 704a-b are respectively
It is connected to multichannel chamber 702 via opening 706a-b.Each opening edge in opening 706a-b
The length multichannel chamber 702 is separately positioned on height h1And h2Place.
Multichannel chamber 702 can be used to measure the various controlled of different liquids in same chamber
Level.Such as, in the case of access road 704b closes relative to air, first liquid
Can be flowed in multichannel chamber 702 by access road 704a.Utilize and reference Fig. 4 A-C
Described similar process, the liquid of scheduled volume can be via access road 704a and 704b phase
It is metered into continuing in multichannel chamber 702.In another embodiment, utilize with reference to figure
Similar process described in 6A-C, a certain amount of first and second liquid stay multichannel chamber
In 702.The amount of the first liquid stayed can correspond to the height h of the first opening 706a1.So
After, access road 704a closes relative to air, and second liquid passes through access road 704b simultaneously
It is flowed in multichannel chamber 702.Furthermore, utilize the similar process having been described above, predetermined
The second liquid of amount is stayed in multichannel chamber 702.The amount of the second liquid stayed can be corresponding
Ground is corresponding to the height h of opening 706b and 706a2And h1Between difference.
Although should be appreciated that and illustrate only two access roades, but any amount of entrance
Passage can realize transmitting liquid at multiple height for the length along multichannel chamber 702
Body.
Fig. 8 show according to another embodiment can be arranged in box housing 102 multiple
Test chamber 216.Each test chamber 216 in multiple test chambers includes access road 302.
Each access road 302 can be connected further to fluid network, such as around testing cassete 102
Fluid network.
Single pressure source (not shown) can be connected to this system so that liquid along multiple enter
Each access road flowing in mouth passage 302.Therefore, it can utilize identical pressure source
Fill each test chamber in multiple test chamber 216.It addition, during applying negative pressure,
The fluid of same predetermined amount can be stayed in each test chamber in multiple test chamber 216.
Same amount of fluid can be stayed in each test chamber 216, and with each access road 302
Between geometrical shape difference unrelated, reason is that each test chamber 216 is similarly pressurizeed.
In another example, liquid can be pressurized in each passage, until being arranged on each
Liquid sensing region in passage, in order to set before by liquid meter to test chamber 216
The liquid of the scheduled volume in fixed each passage.
Fig. 9 shows the multiple test chambers according to another embodiment.Replace each entrance to lead to
Road 901 is connected to single chamber, and each access road 901 includes fluid diverter 902,
Liquid flow is flowed at least two split channel 903a-b.Then, described at least two
Split channel 903a-b can be connected at least two test chamber 904a-b.Although each entrance
Passage is shown in Figure 9 for being diverted in two split channel 903a-b, but in view of this
Literary composition description in the case of, those skilled in the technology concerned should be understood how by any enter
Mouth passage 901 is diverted in other passage any number of.Each split channel 903a-b is permissible
The opening 906a-b arranged via the length along corresponding test chamber is connected to test accordingly
Chamber 904a-b.In one example, each access road 901 can be connected further to stream
Volume grid.
There is provided to multiple test chambers from small number of access road be fed with helping guaranteeing each
Test chamber is contained in the compound of same concentrations present in liquid.Additionally, utilize single enter
Mouth passage reduces the single pressure source of connection to control to each chamber to measure multiple test chambers
The complexity of fluid stream.
Figure 10 shows the analyzer 1001 according to an embodiment, and it carries out operating to perform
The optical detection of the compound in testing cassete system 100.Analyzer 1001 includes optical probe
1002, temperature control component 1004, fan 1006 and include the Photoelectric Detection of object lens 1010
Device unit 1008.
Optical probe 1002 can be aligned above in passage expansion section 214, to detect respective channel
The existence of liquid in chamber.Optical probe 1002 can utilize infrared ray or visible wavelength, and
And include any number of detector and emitter element.It addition, collect from optical probe 1002
To data can be used to other parts of control analyzer 1001.Such as, at optical probe
1002 have been detected by after liquid existed one section of threshold time period, can send signal with
Stop applying normal pressure to liquid and/or utilizing temperature control component 1004 to begin to warm up testing cassete
The content of the test chamber of system 100.
Temperature control component 1004 can be arranged on survey along the base section of testing cassete system 100
Near examination chamber.Temperature control component 1004 can include heating and/or cooling down test chamber
The parts of the content of room.Such as, temperature control component 1004 can be apply thermoelectricity heating or
The Peltier device of cooling.In another example, temperature control component 1004 is resistance heating
Device.Electric current can be through printing coil from the teeth outwards or metal band, with heating of surrounding regions.
In another example, temperature control component 1004 provides forces air, so that survey is heated or cooled
Examination chamber.Force air can be provided by fan 1006.In one embodiment, analyzer
1001 have temperature control component on the both sides of test chamber.Such as, a temperature controls unit
Part may be used for heating, and another temperature control component may be used for cooling.
Photodetector unit 1008 can include known to those skilled in the relevant art any
The fluorescence detector of type, includes but not limited to ccd array, diode and CMOS sensing
Device.In one embodiment, photodetector unit 1008 provides excitation wavelength to test chamber
Light, and collect the fluorescence penetrated by object lens 1010.In another embodiment, by another
Source (not shown) provides excitation wavelength.The fluorescence of injection is along the base section warp of test chamber
Entered region 240 by optics to penetrate from test chamber.
Figure 11 is the flow chart of the chamber fill method 1100 according to an embodiment.
At square frame 1102, the liquid of primary quantity flows along the first access road.First entrance
Passage can be the such as connection entrance 502 shown in Fig. 5.
At square frame 1104, the liquid of primary quantity is divided in multiple second access road, respectively
Individual second access road is connected to multiple test chamber.In one embodiment, multiple test chambers
Each test chamber in room have along chamber length arrange only one opening, with
In receiving in the second access road one.The length of each test chamber can be with gravitational vectors
Generally parallel it is directed at.
At square frame 1106, each test chamber in multiple test chambers is filled with final quantity
Liquid, the liquid of this final quantity is the most equal in each test chamber.It addition, it is every
The liquid of the final quantity in individual test chamber and equal to the liquid of primary quantity.
Other action is considered as equally a part for chamber fill method 1100.Such as,
Chamber fill method 1100 may include that one or more by be arranged in multiple test chamber
One or more reagent in test chamber are resuspended in being metered in each test chamber
Eventually in the liquid of amount.Another exemplary action includes: heat in multiple test chamber at least
Content in one test chamber.This heating can pass through such as Peltier device, resistance
Heating element heater and/or pressure air perform.During chamber fill method 1100, it is also possible to
Detect one or more light of content at least one test chamber in multiple test chamber
Learn characteristic.
Figure 12 is the flow chart of the chamber fill method 1100 according to an embodiment.
At square frame 1202, liquid flows through multiple access road.According to an embodiment, each
Access road is connected to multiple test chamber.The length of each test chamber is basic with gravitational vectors
On be directed at abreast.In one embodiment, each test chamber in multiple test chambers
There is the only one opening of the length setting along chamber.In one example, via single
Pumping source performs the flowing by multiple access roades.
At square frame 1204, each test chamber in multiple test chambers is filled with liquid,
Until threshold quantity.In one example, this threshold quantity is equal to or more than along each test chamber
Length arrange the height residing for opening.
At square frame 1206, by access road by the liquid each survey from multiple test chambers
Examination chamber sucking-off, to leave the liquid of scheduled volume in each test chamber.The liquid of scheduled volume
Can be in along below the height residing for the opening of the length setting of each test chamber
Quantitative liquid.Such as, the amount staying liquid in the chamber can be by gravity and liquid
Surface tension overcomes the position of the negative pressure being applied to passage to be determined.
Other action is considered as equally a part for chamber fill method 1200.Such as,
Chamber fill method 1200 may include that one or more by be arranged in multiple test chamber
One or more reagent in test chamber are resuspended in staying in one or more test chamber
A certain amount of liquid in.If reagent is re-suspended, then perform liquid in square frame 1206
The absorption of body, the speed of absorption does not comprise reagent near the liquid being sufficient so that be drawn.Another
Individual exemplary action includes: that heats at least one test chamber in multiple test chamber is interior
Tolerant.This heating can be by such as Peltier device, stratie and/or pressure sky
Gas performs.During chamber fill method 1200, it is also possible to detect in multiple test chamber
One or more optical characteristics of content at least one test chamber.
The flow chart of the chamber fill method 1200 of another embodiment according to Figure 13.
At square frame 1302, first liquid flows through the first access road.In one embodiment,
First access road is connected to first open along what the length of test chamber was arranged at the first height
Mouthful.The length of test chamber is generally parallel directed at gravitational vectors.At first liquid in side
While flowing through the first access road at frame 1302, the second access road coupled with test chamber
Close relative to air.In one example, both the first and second access roades are when starting
All lead to air.
At square frame 1304, test chamber is filled with first liquid, until first threshold amount.
In one example, first threshold amount is high equal to or more than the first of the first opening of test chamber
Degree.
At square frame 1306, by the first access road by first liquid from test chamber sucking-off,
To leave the liquid of the first scheduled volume in test chamber.The liquid of the first scheduled volume can be with
A certain amount of liquid that the first of first opening of test chamber is highly corresponding.Such as, chamber is stayed
The amount of the liquid in room can be overcome by the surface tension on gravity and liquid be applied to first lead to
The position of the negative pressure in road is determined.
At square frame 1308, according to an embodiment, the first access road is closed relative to air,
And the second access road is opened.Can hold via the one or more valves coupled with fluid network
The switching of row active channels.
At square frame 1310, second liquid flows through the second access road.In one embodiment,
Second access road is connected to the second opening, and this second opening is arranged along the length of test chamber
At second height bigger than first.In one example, via the single pumping source side of execution
The flowing of the second liquid in the flowing of the first liquid in frame 1302 and square frame 1308.
At square frame 1312, test chamber is filled with second liquid, until Second Threshold amount.
At square frame 1314, by the second access road by second liquid from test chamber sucking-off,
To leave the liquid of the second scheduled volume at test chamber.In one example, second scheduled volume
Liquid be and test chamber the second opening second height and the first height of the first opening between
A certain amount of liquid corresponding to difference.In another example, stay the amount of liquid in the chamber
The portion of the negative pressure being applied to second channel can be overcome by the surface tension on gravity and liquid
Position is determined.
Being similar to chamber fill method 1200, other action is considered chamber fill method
The part of 1300.Such as, chamber fill method 1300 may include that and will be arranged on test
The first of the scheduled volume that one or more reagent in chamber are resuspended in staying in test chamber
With in second liquid.Alternatively, one or more reagent described can hang again
Float in the only first liquid staying in test chamber.In one example, in fact it could happen that
Any reagent in test chamber will not be sucked back into first respectively in square frame 1306 and 1314
Or second in access road.Chamber fill method 1300 can also include: heating test chamber
Content and/or one or more optical characteristics of content of detection test chamber, such as pin before
To described in chamber fill method 1200.Although only illustrating in chamber fill method 1300
Two access roades, but it is to be understood that chamber fill method 1300 can expand to include
Lead to any number of access road in one or more chamber.
The flow chart of the chamber fill method 1400 of another embodiment according to Figure 14.
At square frame 1402, according to an embodiment, it is each logical that liquid flows through in multiple passage
Road, until arranging liquid sensing region in each channel.Liquid can be pressurized to along
Each channel flow, and can be individually or simultaneously along each channel flow.According to one
Individual embodiment, make liquid flowing until sensing region set in multiple passage each passage in
The liquid of scheduled volume.
At square frame 1404, according to an embodiment, pre-in each passage in multiple passages
Quantitative liquid is flowed in the corresponding chambers coupled with each passage.Each passage can be independent
Ground or be simultaneously pressurized to the chamber forcing the liquid of scheduled volume to be downwardly into each correspondence.
Method 1400 can also include: will be arranged in the one or more passages in multiple passage
One or more reagent Eddy diffusions.This reagent can be arranged on pre-with what each passage coupled
In first mixing chamber.
The preceding description of specific embodiment will reflect the general characteristic of the present invention completely so that not
In the case of departing from the general concept of the present invention, it is in those skilled in the art's model by application
Enclosing interior knowledge, such specific embodiment easily can be revised and/or be modified to by other people
For various application.Therefore, based on teaching herein and guiding, at such amendment and change
In the equivalent and scope of embodiment disclosed by the invention.Should be appreciated that term herein
Or the purpose that illustrates that of term rather than in order to limit, thus the term of this specification
Should be understood according to teaching and guiding by those skilled in the art with term.
Below describing embodiments of the invention by means of formation function block, these blocks illustrate
The enforcement of specific function and relation thereof.The border of these formation function blocks is in this article in order to say
Bright convenience and optionally limit.Selective border can be limited, as long as can be suitably
Perform specific function and relation thereof.
Summary of the invention and summary part can list or many expected of the present invention by inventor
Individual but be not all, of exemplary embodiment, therefore it is not used to limit by any way the present invention
With appended claim.
The range of the present invention and scope should not limited by any of the above-described exemplary embodiments, but
Should be defined only according to claims below and equivalents thereof.
Claims (72)
1. a fluid test system, comprising:
Multiple test chambers, each test chamber is characterised by that length and hydraulic diameter, each test chamber in wherein said multiple test chambers have the only one opening of the length setting along corresponding test chamber;
First access road, described first access road is configured to the liquid making primary quantity and flows from ingress port, and wherein said ingress port is the described only outside opening of fluid test system;And
Multiple divided fluid stream elements, the plurality of divided fluid stream element is configured to be diverted in multiple second access road along the original liquid of described first access road flowing, only one the second access road that each test chamber in wherein said multiple test chambers is connected in the plurality of second access road via its corresponding opening.
Fluid test system the most according to claim 1, the length of the most each test chamber is configured to be directed at substantially in parallel with gravitational vectors.
Fluid test system the most according to claim 1, it also includes the multiple liquid sensing regions arranged along the plurality of second access road.
Fluid test system the most according to claim 3, each liquid sensing region in wherein said multiple liquid sensing regions is configured to monitor the existence of liquid in corresponding test chamber.
Fluid test system the most according to claim 3, each liquid sensing region in wherein said multiple liquid sensing regions is configured in the liquid meter of scheduled volume to corresponding test chamber.
Fluid test system the most according to claim 1, at least one test chamber in wherein said multiple test chambers includes one or more reagent.
Fluid test system the most according to claim 6, one or more reagent wherein said include the lyophilizing globule being arranged in described test chamber.
Fluid test system the most according to claim 1, it also includes being pre-mixed chamber along what each second access road in the plurality of second access road was arranged.
Fluid test system the most according to claim 8, wherein said multiple chambers that are pre-mixed comprise one or more reagent.
Fluid test system the most according to claim 1, the base wall of each test chamber in wherein said multiple test chambers has the geometry of bending.
11. fluid test systems according to claim 1, the base wall of each test chamber in wherein said multiple test chambers is transparent, to allow to be optically inspected.
12. fluid test systems according to claim 1, the most single pump is configured to pass the first access road so that the liquid of primary quantity, and each test chamber in the plurality of test chamber is filled with the liquid of equal quantities.
13. fluid test systems according to claim 1, one or more walls of plurality of chamber contact with the housing of thermal control.
14. fluid test systems according to claim 13, wherein said one or more walls are the polymeric films that thickness is less than 100 microns.
15. fluid test systems according to claim 13, the thermal conductivity of wherein said one or more walls is more than 1W/mK.
16. fluid test systems according to claim 13, the housing of wherein said thermal control includes Peltier device.
17. fluid test systems according to claim 13, the housing of wherein said thermal control includes stratie.
18. fluid test systems according to claim 13, the housing of wherein said thermal control heats via pressure air.
19. 1 kinds of chamber fill methods, comprising:
Make the liquid first access road flowing along single port fluid test system of primary quantity;
The liquid of described primary quantity is diverted to multiple second access road from described first access road, each second access road is connected to multiple test chamber, and each test chamber in wherein said multiple test chambers has the only one opening of the length setting along chamber;And
Each test chamber in the plurality of test chamber is filled with the liquid of final quantity, and the final quantity in each test chamber is substantially identical, and the liquid of the final quantity of each test chamber and equal to the liquid of described primary quantity.
20. methods according to claim 19, the length of the most each test chamber is configured to be directed at substantially in parallel with gravitational vectors.
21. methods according to claim 19, it also includes: be resuspended in the liquid of described final quantity by one or more reagent being arranged in the one or more test chambers in the plurality of test chamber.
22. methods according to claim 19, it also includes: be resuspended in being arranged on multiple one or more one or more reagent being pre-mixed in chamber being pre-mixed in chamber in the liquid of described final quantity.
23. methods according to claim 19, it also includes heating steps: the content at least one test chamber heating in the plurality of test chamber.
24. methods according to claim 23, wherein said heating steps includes utilizing Peltier device to heat.
25. methods according to claim 23, wherein said heating steps includes utilizing stratie to heat.
26. methods according to claim 23, wherein said heating steps includes utilizing forces air to heat.
27. methods according to claim 19, it also includes one or more optical characteristics of the content at least one test chamber detecting in the plurality of test chamber.
28. methods according to claim 19, wherein via single pumping source execution flows, shunt and fill.
29. 1 kinds of fluid test systems, comprising:
Multiple test chambers, each test chamber is characterised by length and hydraulic diameter, the length of the most each test chamber is configured to be directed at substantially in parallel with gravitational vectors, and each test chamber in wherein said multiple test chamber has the only one opening of the length setting along corresponding test chamber;
Multiple access roades, the only one access road that each test chamber in wherein said multiple test chambers is connected in the plurality of access road via its corresponding opening;And
Fluid network, described fluid network is configured to be connected to the plurality of access road other chamber one or more.
30. fluid test systems according to claim 29, it also includes the multiple liquid sensing regions arranged along the plurality of access road.
31. fluid test systems according to claim 30, each liquid sensing region in wherein said multiple liquid sensing regions is configured to monitor the existence of liquid in corresponding test chamber.
32. fluid test systems according to claim 30, each liquid sensing region in wherein said multiple liquid sensing regions is configured in the liquid meter of scheduled volume to corresponding test chamber.
33. fluid test systems according to claim 29, wherein remaining liquid by corresponding access road after the only one opening of the length along corresponding test chamber is sucked out, the amount of the liquid in corresponding chambers is stayed in the position control of described only one opening.
34. fluid test systems according to claim 29, the width of wherein said only one opening is more than the width of corresponding access road.
35. fluid test systems according to claim 29, at least one test chamber in wherein said multiple test chambers includes one or more reagent.
36. fluid test systems according to claim 35, one or more reagent wherein said include the lyophilizing globule being arranged in described test chamber.
37. fluid test systems according to claim 29, it also includes being pre-mixed chamber along what each second access road in the plurality of second access road was arranged.
38. according to the fluid test system described in claim 37, and the wherein said chamber that is pre-mixed comprises one or more reagent.
39. fluid test systems according to claim 29, the base wall of each test chamber in wherein said multiple test chambers has the geometry of bending.
40. fluid test systems according to claim 29, the base wall of each test chamber in wherein said multiple test chambers is transparent, to allow to be optically inspected.
41. fluid test systems according to claim 29, the most single pump is used for making liquid pass the plurality of access road.
42. fluid test systems according to claim 29, one or more walls of plurality of chamber contact with the housing of thermal control.
43. fluid test systems according to claim 42, wherein said one or more walls are the polymeric films that thickness is less than 100 microns.
44. fluid test systems according to claim 42, the thermal conductivity of wherein said one or more walls is more than 1W/mK.
45. fluid test systems according to claim 42, the housing of wherein said thermal control includes Peltier device.
46. fluid test systems according to claim 42, the housing of wherein said thermal control includes stratie.
47. fluid test systems according to claim 42, the housing of wherein said thermal control heats via pressure air.
48. fluid test systems according to claim 29, at least one access road in wherein said multiple access roades is connected to more than one opening.
49. 1 kinds of chamber fill methods, comprising:
Flow liquid through multiple access road, each access road is connected to multiple test chamber, the length of the most each test chamber is configured to be directed at substantially in parallel with gravitational vectors, and each test chamber in wherein said multiple test chamber has the only one opening of the length setting along chamber;
Each test chamber in the plurality of test chamber is filled with liquid, until threshold quantity;
By described access road by the liquid each test chamber sucking-off from the plurality of test chamber, the most this sucking-off leaves the liquid of scheduled volume in each test chamber.
50. methods according to claim 49, it also includes: be resuspended in a certain amount of liquid staying in the one or more test chamber by one or more reagent being arranged in the one or more test chambers in the plurality of test chamber.
51. methods according to claim 50, the liquid not comprising reagent is drawn in wherein said sucking-off.
52. methods according to claim 49, wherein fill and include filling each test chamber until threshold quantity until a height, and described height is equal to or more than the height residing for the opening along the length setting of each test chamber.
53. methods according to claim 52, wherein stay the liquid of scheduled volume to include leaving a certain amount of liquid being in along below the height residing for the opening of the length setting of each test chamber.
54. methods according to claim 49, it also includes heating steps: the content at least one test chamber heating in the plurality of test chamber.
55. methods according to claim 54, wherein said heating steps includes utilizing Peltier device to heat.
56. methods according to claim 54, wherein said heating steps includes utilizing stratie to heat.
57. methods according to claim 54, wherein said heating steps includes utilizing forces air to heat.
58. methods according to claim 49, it also includes one or more optical characteristics of the content at least one test chamber detecting in the plurality of test chamber.
59. methods according to claim 49, wherein via single pumping source execution flows.
60. 1 kinds of chamber fill methods, comprising:
Making first liquid flow through the first access road, described first access road is connected to be arranged on the first opening at the first height along the length of test chamber, and the length of wherein said test chamber is configured to be directed at substantially in parallel with gravitational vectors;
Described test chamber is filled with first liquid, until first threshold amount;
By described first access road by described first liquid from described test chamber sucking-off, wherein said sucking-off leaves the first liquid of the first scheduled volume in described test chamber;
Making second liquid flow through the second access road, described second access road is connected to be arranged on the second opening at the second height along the length of described test chamber, and wherein said second height is more than described first height;
Described test chamber is filled with described second liquid, until Second Threshold amount;
By described second access road by described second liquid from described test chamber sucking-off, wherein said sucking-off leaves the second liquid of the second scheduled volume in described test chamber.
61. methods according to claim 60, wherein stay the first liquid of the first scheduled volume to include leaving a certain amount of first liquid the most corresponding with the first of described first opening.
62. methods according to claim 61, wherein stay the second liquid of the second scheduled volume to include leaving a certain amount of second liquid corresponding with the difference between the second of described second opening the height and the first height of described first opening.
63. methods according to claim 60, it also includes: be resuspended in staying by one or more reagent being arranged in described test chamber in first liquid and the second liquid of the scheduled volume in described test chamber.
64. methods according to claim 60, it also includes: be resuspended in staying in the first liquid of the only scheduled volume in described test chamber by one or more reagent being arranged in described test chamber.
65. methods according to claim 64, wherein sucking-off first liquid or second liquid draw the liquid not comprising any reagent.
66. methods according to claim 60, it also includes heating steps: heat the content in described test chamber.
67. methods according to claim 66, wherein said heating steps includes utilizing Peltier device to heat.
68. methods according to claim 66, wherein said heating steps includes utilizing stratie to heat.
69. methods according to claim 66, wherein said heating steps includes utilizing forces air to heat.
70. methods according to claim 60, its one or more optical characteristics also including detecting the content in described test chamber.
71. methods according to claim 60, wherein perform first liquid and the flowing of second liquid via single pumping source.
72. methods according to claim 60, it also includes: after sucking-off first liquid, closed relative to air by described first access road.
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